Pathogenesis of autoimmunity in alphabeta T cell-deficient lupus-prone mice.
Murine lupus in MRL mice has been strongly attributed to alphabeta T cell-dependent mechanisms. Non-alphabeta T cell-dependent mechanisms, such as gammadelta T cells, have been shown to drive antibody and autoantibody production, but they have not been considered capable of inducing end-organ disease. Here, we have expanded upon the findings of such previous work by examining the mechanism and extent of end-organ disease attainable via gammadelta T cells and/or non-alphabeta T cell-dependent mechanisms, assessing two prototypical lupus lesions, renal and skin disease, in TCR alpha -/- MRL mice that possessed either functional or defective Fas antigen (Fas + or lpr). Observed to 1 year of age, TCR alpha -/- MRL mice developed disease characterized by increased mortality, overt renal disease and skin lesions. While delayed in onset and/or reduced in severity compared with TCR alpha +/+ MRL/lpr animals, renal and skin lesions in alphabeta T cell-deficient animals were clearly increased in severity compared with age-matched control non-autoimmune mice. In contrast to TCR alpha +/+ MRL mice, whose disease reflected pan-isotype immune complex deposition with significant complement fixation, renal disease in TCR alpha -/- MRL animals reflected predominantly IgG1 immune complex deposition, with poor complement fixation. Thus, this study demonstrates conclusively that non-alphabeta T cell-dependent mechanisms can induce renal and skin injury in murine lupus, but at least in the kidney, only via humoral autoimmunity of a relatively non-pathological isotype which results in the delayed onset of end-organ damage.
Peng
S L
SL
Section of Rheumatology, Yale University School of Medicine, New Haven, CT, USA.
Cappadona
J
J
McNiff
J M
JM
Madaio
M P
MP
Owen
M J
MJ
Hayday
A C
AC
Craft
J
J
D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D007674:Kidney Diseases / Q000276:immunology / Q000473:pathology; D008177:Lupus Vulgaris / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta